Stroke propensity in the Th3+/ mouse model of β-thalassemia intermedia.
Stroke propensity in the Th3+/ mouse model of β-thalassemia intermedia.
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DOI：
10.1016/j.nbd.2022.105802
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发表时间：
2022-09
影响因子：
6.1
通讯作者：
Kuan, Chia-Yi
中科院分区：
文献类型：
--
作者：
Sun, Yu-Yo;Yao, Hui-Wen;Chen, Hong-Ru;Chen, Ching-Wen;Kinkaid, Melissa M.;Kuan, Chia-Yi
关键词：
β-地中海贫血与多种血液学和脑血管症状有关，而这些症状与高凝状态有关，而这种状态尚未在用于开发中风治疗的动物模型中完全复制。在此，我们比较了 6 个月大的野生型和杂合 Th3/+ 小鼠（非输血依赖性中间型 β-地中海贫血（β-TI）模型）的生理特性和对短暂性脑缺氧缺血（tHI）的反应。我们发现 Th3/+ 小鼠出现小细胞性贫血、脾肿大、血小板计数升高以及血小板-红细胞和红细胞-白细胞聚集体增加。此外，Th3/+小鼠在重复的高碳酸血症挑战下表现出脑血管反应性（CVR）和皮质氧饱和度降低。当受到低于阈值的 tHI 损伤时，Th3/+ 小鼠中的血小板和白细胞会粘附在脑血管壁上或形成聚集体，而野生型小鼠中的血小板和白细胞则能顺利飞过。随后，Th3/+小鼠表现出比野生型小鼠脑血管周围纤维蛋白沉积增加和更大的梗塞，尤其是雌性Th3/+小鼠。总的来说，这些结果表明 Th3/+ 小鼠模仿 β-TI 患者的关键临床特征和血栓栓塞倾向。 Th3/+ 小鼠的高凝状态可能是由多种血液学和 CVR 异常引起的，这些异常与镰状细胞性贫血小鼠模型相似但不相同。因此，我们认为 Th3/+ 小鼠是研究地中海贫血患者的病理机制和预防性中风治疗的有用模型。
β-thalassemia is associated with multiple hematological and cerebrovascular symptoms linked to a hypereoagulable state that has not been fully replicated in animal models for the development of stroke treatments. Herein we compared the physiological properties and responses to transient cerebral hypoxia-ischemia (tHI) between six-month-old wildtype and heterozygous Th3/+ mice, a model of non-transfusion-dependent β-thalassemia intermedia (β-TI). We found that Th3/+ mice developed microcytic anemia, splenomegaly, higher platelet counts, and increased platelet-erythrocyte plus erythrocyte-leukocyte aggregates. Furthermore, Th3/+ mice showed diminished cerebrovascular reactivity (CVR) and cortical oxygen saturation under repetitive hypercapnic challenges. When subjected to a sub-threshold tHI insult, platelets and leukocytes in Th3/+ mice adhered to the cerebrovascular wall or formed aggregates, while their counterparts flew through smoothly in wildtype mice. Subsequently, Th3/+ mice showed increased fibrin deposition around cerebral blood vessels and larger infarction than wildtype mice, especially in female Th3/+ mice. Collectively these results showed that Th3/+ mice mimic key clinical features and a propensity to thromboembolism in β-TI patients. The hypereoagulable state in Th3/+ mice is likely caused by multiple hematological and CVR anomalies that are similar, but are not identical to those in the mouse model of sickle cell anemia. As such, we suggest that Th3/+ mice are a useful model to study the pathological mechanisms and prophylactic stroke treatments in thalassemia patients.
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影响因子：
20.3
作者：
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通讯作者：
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影响因子：
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发表时间：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1161/atvbaha.110.211615
发表时间：
2010-12
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Polanowska-Grabowska R;Wallace K;Field JJ;Chen L;Marshall MA;Figler R;Gear AR;Linden J
通讯作者：
Linden J